5,808 research outputs found

    Assessing Consistency and Fairness in Sentencing: A Comparative Study in Three States

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    Summarizes a study of sentencing guidelines in Michigan, Minnesota, and Virginia comparing levels of predictability and judicial discretion under different guideline systems, effectiveness in limiting discriminatory disparities, and lessons learned

    From farmers' fields to data fields and back: A Synthesis of Participatory Information Systems for Irrigation and other Resources: Proceedings of an International Workshop held at the Institute of Agriculture and Animal Science, Rampur, Nepal, 21-26 March 1993

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    Irrigation / Forestry / Natural resources / Farmer participation / Participatory rural appraisal / Rapid rural appraisal / GIS / Data collection / Databases / Field tests / Farmers' associations / Training / Water rights / Water law / Institutions / Non-governmental organizations / India / Nepal

    Economic Analysis, Sustainability and Environmental Commons

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    When confronted with market weaknesses and failures determining sustainability problems for environmental common-pool resources, economic analysis has proposed government intervention as the only alternative available. Elinor Ostrom showed that this dichotomy between market and government is not always helpful, and proposed a more complex approach to institutions focusing on an active role of communities, social norms and a polycentric system of governance. This paper summarizes the main factors at work in determining the role of institutions to deal with sustainability issues and explores the implications of this wider approach in dealing with environmental commons, particularly with global environmental commons, discussing two issues: climate change and biodiversity. Involvement of governments and a reference framework provided by intergovernmental agreements are necessary, but the difficulties of building a successful intergovernmental institutional framework require responsible and convinced actions at the level of consumers and firms, public opinion involvement in individual countries, and coordination between local and national levels of government: provided that some conditions are fulfilled, common resource management can be very helpful in achieving them

    Activation of Adenylyl Cyclase Reduces TGF-b Profibrotic Response in Osteoarthritic Fibroblast-like Synoviocytes

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    Purpose: The hallmarks of osteoarthritis (OA) include cartilage degeneration, bone remodeling and synovial fibrosis. Synovial fibrosis is characterized by excessive extracellular matrix (ECM) accumulation due to an imbalance in ECM production, in particular collagen, and its turnover. Transforming growth factor beta (TGF-β) and its associated signaling pathway mediated by ALK5, plays an important role in synovial fibrosis and blocking TGF-β’s effect prevents synovial fibrosis. Increasing intracellular cyclic AMP (cAMP) produces an antifibrotic effect in fibroblasts of multiple origins. Forskolin (FsK) is a naturally occurring diterpene in the roots of the Indian Coleus plant that activates adenylyl cyclase resulting in an elevation in intracellular cAMP levels. We hypothesized that FsK treatment results in an anti-fibrotic effect in TGF-β stimulated fibroblast-like synoviocytes (FLS) from patients with advanced OA. Methods: OA FLS (Cell Applications, USA) were harvested from patients undergoing total knee replacement. Cells were used between the 3rd and 6th passages for all experiments. OA FLS (300,000 cells per well) were treated with TGF-β (1ng/ml; R&D Systems) in the absence or presence of FsK (10μM; Sigma Aldrich) or SB431542, an ALK5 inhibitor (1μM, Sigma Aldrich) for 24 hours followed by RNA extraction using Trizol reagent and RNA concentrations were determined using a NanoDrop ND-2000 spectrophotometer. cDNA was synthesized using iScript Reverse Transcription Supermix for RT-qPCR (Bio-Rad, USA). Quantitative PCR (qPCR) was performed using TaqMan Fast Advanced Master Mix (Lifetechnologies, USA). The cycle threshold (Ct) value of genes of interest were normalized to the Ct value of GAPDH in the same sample, and the relative expression was calculated using the 2−ΔΔCt method. Genes of interest included collagens type 1 (COL1A1) and 3 (COL3A1), α2 smooth muscle actin (ACTA2), proteoglycan-4 (PRG4), matrix metalloproteinases 3, 9 and 13 (MMP3, MMP9 and MMP13), tissue inhibitor of metalloproteinase-1 (TIMP1) and aggrecanase-1 (ADAMTS4). Multiple group comparisons were performed by ANOVA or ANOVA on the ranks followed by pairwise group comparisons using Tukey\u27s test. Data is presented as the average ± S.D. of 3–6 independent experiments. Results:FsK treatment significantly reduced TGF-β induced expression of collagen type I (fig. 1A; p Conclusions: Using a model of TGF-β stimulated OA synovial fibroblasts, FsK treatment resulted in a reduction in the expression of collagen type I, a major component of fibrosis and α2 smooth muscle actin, a marker of fibroblast differentiation to myofibroblasts. To this end, FsK\u27s effect was comparable to the inhibition of intracellular TGF-β signaling. PRG4 regulates synovial proliferation and inflammation and FsK treatment enhanced PRG4 expression by OA fibroblasts. FsK reduced expression of matrix degrading enzymes, especially MMP3 and MMP9 involved in synovial proliferation, and MMP13 and ADAMTS4, involved in cartilage degradation. Increasing intracellular levels of cAMP in synovial fibroblasts may result in antifibrotic and chondroprotective effects in the joint

    Arabian Sea mixed layer dynamics experiment : mooring deployment cruise report R/V Thomas Thompson cruise number 46, 14 April-29 April 1995

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    This report describes in a general manner the work that took place during the R/V Thomas Thompson cruise number 46 which was the mooring turnaround cruise for the moored array program. A detailed description of the WHOI surface mooring and its instrumentation is provided. Information about the XBT and CTD data and near-surface temperature data collected during the cruise is also included.Funding was provided by the Office of Naval Research through Grant No. NOOOl4-94-1-0161
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